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181.
Kata Horváti Gábhor Mező Nóra Szabó Ferenc Hudecz Szilvia Bősze 《Journal of peptide science》2009,15(5):385-391
Tuberculosis (TB) is a bacterial infectious disease caused by Mycobacterium tuberculosis, a slow‐growing, powerful human pathogen which can survive in the host macrophages. In the chemotherapy of such intracellular pathogens it is necessary to achieve relatively high level of the drug in blood to attain therapeutically effective concentration in infected cells, which presumably has several serious side effects on healthy tissues. The elimination of M. tuberculosis from infected phagocytes could be more efficient with target cell‐directed delivery of antituberculars. A particularly promising approach is to conjugate a drug moiety to a peptide based carrier. The conjugates are chemically constructed to target release by hydrolysis (enzymatic and/or chemical) to liberate the active compound. Here we report the synthesis, characterisation and antimycobacterial evaluation of isoniazid (INH) peptide conjugates. As carrier moiety T‐cell epitope of immundominant 16‐kDa protein of M. tuberculosis and tuftsin‐derived peptides were used. To conjugate INH two synthetic methods were developed, where INH was coupled directly to the peptides or through a heterobifunctional reagent. We found that all of the INH conjugates were effective against M. tuberculosis and the minimal inhibitory concentration (MIC) values were comparable to the free INH moiety. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
182.
Orsolya Toke Zoltán Bánóczi Gábor Tárkányi Péter Friedrich Ferenc Hudecz 《Journal of peptide science》2009,15(6):404-410
Calpastatin, the endogenous inhibitor of calpain, a cysteine protease in eukaryotic cells, is an intrinsically unstructured protein, which upon binding to the enzyme goes through a conformational change. Peptides calpA (SGKSGMDAALDDLIDTLGG) and calpC (SKPIGPDDAIDALSSDFTS), corresponding to the two conserved subdomains of calpastatin, are known to activate calpain and increase the Ca2+ sensitivity of the enzyme. Using solution NMR spectroscopy, here we show that calpA and calpC are disordered in water but assume an α‐helical conformation in 50% CD3OH. The position and length of the helices are in agreement with those described in the literature for the bound state of the corresponding segments of calpastatin suggesting that the latter might be structurally primed for the interaction with its target. According to our data, the presence of Ca2+ induces a backbone rearrangement in the peptides, an effect that may contribute to setting the fine conformational balance required for the interaction of the peptides with calpain. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
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184.
In this study the possible effects of two predicted climate change scenarios on soil water regime of Hungarian Calcic Chernozem
soils has been investigated. Soil profiles classified as Calcic Chernozem — in total 49 — were selected from the MARTHA soil
physical database that incorporates soil data at national scale. These profiles were subdivided into three groups (sandy loam,
loam and clayey loam) in accordance with their mechanical composition. Soil water retention curves were scaled separately
for each of the three textural groups, using similar media scaling in order to represent the variability of soil hydrophysical
data with one parameter, the scaling factor (SF). Reference soil profiles were chosen according to the cumulative distribution
function of the scaling factor, six for each textural group. Daily downscaled meteorological data from A2 and B2 climate scenarios
of the Hadley Centre (2070–2100) and data from a reference period (RF, 1961–1990) were used in this study to characterize
different climatic situations. Nine representative years were selected in case of all the three scenarios, using the cumulative
probability function of the annual precipitation sum. Scenario analyses were performed, validating the SWAP soil water balance
simulation model for the 18 reference soil profiles and 27 representative years in order to evaluate the expected changes
in soil water regime under different from the present (RF) climatic conditions (A2 and B2 scenarios). Our results show that
the scaling factor could be used as a climate sensitivity indicator of soil water regime. The large climate sensitivity of
the majority of Chernozem soil subtypes water regime has been proven. 相似文献
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186.
Péterfia B Hollósi P Szilák L Timár F Paku S Jeney A Kovalszky I 《Magyar onkologia》2006,50(2):115-120
Syndecan-1 is a transmembrane heparan sulfate proteoglycan which plays pivotal role in cell-cell and cell-extracellular matrix interactions. However, its implication in the establishment of malignant phenotype is still controversial. Its expression indicates differentiated phenotype in certain tumors, while it confers invasive nature for others. For the better understanding of the role of syndecan-1 in cancer we transfected HT-1080 fibrosarcoma cell line with the full and a truncated construct of syndecan-1 and established stable cell lines with them. We studied the in vitro and in vivo growth capacity and metastatic potential of the transfectants in comparison with the cell line bearing only the EGFP expression vector. Our results showed that the growth rate of syndecan transfectants increased and they developed more lung metastases than the control cells. As local growth of the full transfectant was faster than that of the 78sig we presume that the full protein and maybe the shedding is needed for the local development of the tumor, but the intracellular and transmembrane domain is sufficient to promote metastasis formation. 相似文献
187.
Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?
Papp M Norman GL Vitalis Z Tornai I Altorjay I Foldi I Udvardy M Shums Z Dinya T Orosz P Lombay B Par G Par A Veres G Csak T Osztovits J Szalay F Lakatos PL 《PloS one》2010,5(9):e12957
Background
Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn''s disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections.Methodology/Principal Findings
Sera of 676 patients with various chronic liver diseases (autoimmune diseases:266, viral hepatitis C:124, and liver cirrhosis of different etiology:286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae(ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR:1.62, 95%CI:1.16–2.25), co-morbidities (OR:2.22, 95%CI:1.27–3.86), and ASCA positivity (OR:1.59, 95%CI:1.07–2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR:1.85) and co-morbidities (p<0.001, OR:2.02) by Cox-regression analysis.Conclusions/Significance
The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies. 相似文献188.
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190.
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays a crucial role in differentiation of oligodendrocytes. Here we first demonstrated by multinuclear NMR that the extended disordered segments are localized at the N- and C-terminals straddling a flexible region. We showed by affinity chromatography, fluorescence spectroscopy and circular dichroism that GTP binds to TPPP/p25 likely within the flexible region; neither positions nor intensities of the peaks in the assigned terminals were affected by GTP. In addition, we demonstrated that TPPP/p25 specifically hydrolyses GTP in an Mg(2+)-dependent manner. The GTPase activity is comparable with the intrinsic activities of small G proteins suggesting its potential role in multiple physiological processes. 相似文献